Original article| Volume 45, 102389, October 2020

Apolipoproteins AI and E are associated with neuroaxonal injury to gray matter in multiple sclerosis


      • Cholesterol biomarkers association with serum neurofilaments in MS were studied.
      • Serum neurofilaments were associated with apolipoprotein E at 5-year follow-up.
      • Apolipoprotein E4 allele was associated with greater serum neurofilaments.
      • Increased HDL associated with less gray matter and cortical atrophy.
      • Cholesterol biomarkers associations remain after adjusting for serum neurofilaments.


      Purpose To investigate the associations between longitudinal changes in lipid biomarkers and serum neurofilament (sNfL) levels in multiple sclerosis (MS) neurodegeneration and disease progression.
      Methods 5-year prospective, longitudinal study included 75 relapsing-remitting MS (RR-MS) and 37 progressive-MS (P-MS) patients. sNfL, plasma total cholesterol (TC), high-density (HDL-C) and low-density (LDL-C) lipoprotein cholesterol, apolipoproteins (Apo), ApoA-I, Apo-II, ApoB, ApoC-II and ApoE were measured at baseline and 5-years. Annual percent changes in whole brain volume (PBVC), gray matter volume (PGMVC) and cortical volume (PCVC) were obtained from MRI at baseline and 5-years.
      Results sNfL levels at 5-year follow-up were associated with ApoE at follow-up (p = 0.014), age at follow-up, body mass index (p < 0.001) and RR vs. P-MS status at follow-up. APOE4 allele was associated with greater sNfL levels at 5-years (p = 0.022) and pronounced in the P-MS group. PGMVC and PCVC were associated with percent changes in HDL-C (p = 0018 and p < 0.001, respectively) and ApoA-I (p = 0.0073 and p = 0.006). PGMVC and PCVC remained associated with percent change in HDL-C (p = 0.0024 and p < 0.001, respectively) after sNfL was included as a predictor.
      Conclusions HDL-C percent change is associated with decreased gray matter atrophy after adjusting for baseline sNfL.


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